LIVER TRANSPLANTATION 20:1157–1167, 2014

ORIGINAL ARTICLE

Analysis of Factors Associated With Portal Vein Thrombosis in Pediatric Living Donor Liver Transplant Recipients  Joao Seda Neto,1,2 Eduardo A. Fonseca,1,2 Flavia H. Feier,1,2 Renata Pugliese,1,2 Helry L. Candido,1,2 1,2 1,2 Marcel R. Benavides, Gilda Porta, Irene K. Miura,1,2 Vera B. Danesi,1,2 Teresa Guimaraes,1,2 Adriana Porta,1,2 Cristian Borges,1,2 Andre Godoy,2 Mario Kondo,1,2 and Paulo Chapchap1 1 ~ Paulo, Brazil; and 2A. C. Camargo Hepatology and Liver Transplantation, Hospital Sirio-Libanes, Sao ~ Cancer Center, Sao Paulo, Brazil

The technique of vascular reconstruction plays a major role in the outcome of living donor liver transplantation (LDLT). An increased use of vascular grafts (VGs) as replacements for sclerotic portal veins has become a standard technique for our group. The aim of this study was to analyze the factors associated with portal vein thrombosis (PVT) in pediatric LDLT. We performed a retrospective analysis of 486 primary pediatric LDLT procedures performed between October 1995 and May 2013. VGs used for portal reconstruction included living donor inferior mesenteric veins, living donor ovarian veins, recipient internal jugular veins, deceased donor iliac arteries, and deceased donor iliac veins. Thirty-four patients (7.0%) developed PVT. The incidence of PVT dropped from 10.1% to 2%; the overall utilization of VGs increased from 3.5% to 37.1%. In a multivariate analysis, only the use of VGs remained an independent risk factor for the occurrence of PVT (hazard ratio 5 7.2, 95% confidence interval 5 2.8-18.7, P < 0.001). There was no difference in survival rates between patients with PVT and patients without PVT. No patient with PVT underwent retransplantation. In conclusion, the use of VGs was independently associated with the development of PVT. Over time, there was a reduction in the incidence of early PVT in this cohort, and there was a trend toward a reduction in total PVT. The occurrence of isolated PVT in this study was not associC 2014 AASLD. ated with decreased patient or graft survival. Liver Transpl 20:1157-1167, 2014. V Received January 30, 2014; accepted June 2, 2014. Pediatric liver transplantation performed with either deceased or living donors demands a refined surgical technique because of the small caliber of the vascular and biliary structures. The transplantation of partial liver grafts involves additional technical difficulties because it uses short vascular pedicles, which are more likely to cause postoperative vascular complications,1 and because the size of these pedicles is dis-

crepant with the recipient vascular structures. Additionally, biliary atresia (BA), the leading indication for transplantation in children, is associated with portal vein (PV) sclerosis, which can result in added difficulties during vascular reconstruction in this population. The use of vascular grafts (VGs) to replace the existing sclerotic PV in cases of BA was described after the

Abbreviations: BA, biliary atresia; BW, body weight; DDIA, deceased donor iliac artery; DDIV, deceased donor iliac vein; e-PVT, early portal vein thrombosis; GRWR, graft-to-recipient weight ratio; HA, hepatic artery; HAT, hepatic artery thrombosis; IR, interventional radiology; LDIMV, living donor inferior mesenteric vein; LDLT, living donor liver transplantation; LDOV, living donor ovarian vein; l-PVT, late portal vein thrombosis; MRI, magnetic resonance imaging; PELD, Pediatric End-Stage Liver Disease; PRBC, packed red blood cell; PV, portal vein; PVC, portal vein complication; PVT, portal vein thrombosis; RIJV, recipient internal jugular vein; SMV, superior mesenteric vein; SR, splenorenal; SV, splenic vein; t-PVT, total portal vein thrombosis; US, ultrasound; VG, vascular graft. Potential conflict of interest: Nothing to report. There were no sources of financial support. Address reprint requests to Joao Seda Neto, M.D., Ph.D., Hepatology and Liver Transplantation, Hospital Sirio-Libanes, Rua Barata Ribeiro ~o Paulo, Brazil 01308-000. Telephone: 55-11-32310800; FAX: 55-11-32310900; E-mail: [email protected] 414, cj 65, Bela Vista, Sa DOI 10.1002/lt.23934 View this article online at wileyonlinelibrary.com. LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases

C 2014 American Association for the Study of Liver Diseases. V

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initial experience with partial liver graft transplantation using either living or deceased donors.2-4 The use of a deceased donor iliac vein (DDIV) and a saphenous vein was originally described for interposition to the recipient’s portal system,4 but the availability of VGs retrieved from living donors is in part restricted to the living donor inferior mesenteric vein (LDIMV) or the living donor ovarian vein (LDOV) and to the recipient internal jugular vein (RIJV).5-7 The largest experience with pediatric living donor liver transplantation (LDLT) described so far with an emphasis on portal vein complications (PVCs) comes from the Kyoto group.5 The important part of this group’s publication is the description of 5 different strategies for PV reconstruction in pediatric LDLT using left-sided liver grafts. Indeed, it is an update of a technique previously described by the same group reported 10 years earlier.2 Interestingly, the types of VGs used for portal reconstruction in the 2 reports were the LDIMV and the LDOV. The use of such grafts was not associated with the occurrence of PVCs, and the only risk factor was a recipient’s body weight (BW) less than 6 kg. The aims of this retrospective study were to analyze the factors associated with portal vein thrombosis (PVT) in primary pediatric LDLT, to describe the types of PV reconstructions used in this series, and to evaluate the outcomes of such patients.

PATIENTS AND METHODS Patients From October 1995 to May 2013, 505 primary LDLT procedures in all were performed in patients less than 18 years of age at the Hospital Sirio Libanes and the ~ o Paulo, BraA. C. Camargo Cancer Center (both in Sa zil). The patients were managed by the same medical group at both hospitals. Data on transplant recipients were collected through retrospective examinations of medical records and from a prospectively collected database. Patients who developed hepatic artery thrombosis (HAT) were excluded from this report. The hospitals’ ethics committees approved this study. The evaluation of the liver transplant recipients followed standard procedures, including the investigation of the etiology and severity of the liver disease; imaging studies when applicable [Doppler ultrasound (US), computerized tomography, or magnetic resonance imaging (MRI)]; and dental, psychological, and nutritional evaluations. Recipient/donor selection was based on ABO compatibility. Pediatric patients with end-stage liver disease who were accepted by the transplant team for liver transplantation were initially placed on the waiting list for deceased donor liver transplantation. The preoperative donor evaluation and the surgical techniques have been described in previous publications.6,7 The age limit and the highest body mass index accepted for donation were 50 years and 28 kg/ m2, respectively. Doppler US was performed to evalu-

LIVER TRANSPLANTATION, October 2014

ate the vascular anatomy, liver echogenicity (the presence of steatosis and the detection of parenchymal lesions), and liver volumetry for left lateral segment donation. MRI and cholangio-MRI were used to assess the anatomy for left lobe and right lobe donation.

Back-Table Preparation After the completion of the donor hepatectomy, each graft was flushed through the PV and the hepatic artery (HA) with a preservation solution (30 mL/g; Euro-Collins or histidine tryptophan ketoglutarate solution) at 4 C. A careful dissection of the PV was performed to increase its length and facilitate graft implantation during the recipient operation.

Recipient Operation Grafts were implanted with the piggyback technique. The graft hepatic veins were anastomosed to the recipient vena cava/hepatic veins in a fashion similar to that previously described.1 The anastomoses were performed with continuous 6-0 Prolene sutures, regardless of the type of implant. The graft’s PV was anastomosed in an end-to-end fashion with continuous 7-0 Prolene sutures either to the recipient’s PV trunk (Fig. 1A) or with an interposition VG (Fig. 1B). The VGs were filled with a heparinized solution after the completion of the anastomoses. Different VGs were used for PV reconstruction, and they were obtained from the LDIMV, LDOV, RIJV, DDIV, or deceased donor iliac artery (DDIA). The technique was used to minimize the size discrepancy between the vascular anastomoses used for portal reconstruction. Figure 2 exemplifies PV reconstruction with the interposition of an LDIMV (Fig. 2A) or a DDIA (Fig. 2B). The HA was always reconstructed with microvascular techniques and 9-0 or 10-0 nylon sutures (Ethicon, Edinburgh, United Kingdom). Finally, the biliary anastomosis was performed either as a duct-to-duct or Roux-in-Y bilioenteric reconstruction.

Postoperative Management and Anticoagulation Doppler US scans were routinely performed on postoperative day 1 to evaluate the vascular patency. Immunosuppression was based on tacrolimus (Prograf) and steroids. Details on the postoperative clinical management have been previously reported.6,7 Postoperative anticoagulation throughout the study period was restricted to patients who presented with intraoperative vascular thrombosis or patients with BuddChiari syndrome. It was based on an intravenous infusion of heparin with a starting dose of 10 U/kg/ hour. The heparin infusion was then tapered for a partial thromboplastin time 2 to 3 times the normal range. Patients with Budd-Chiari syndrome were kept on oral anticoagulation with a target international normalized ratio between 2 and 3. All patients with platelet counts > 50,000/mm3 were kept on dipyridamole (1 mg/kg/day) for 3 months after the transplant.

LIVER TRANSPLANTATION, Vol. 20, No. 10, 2014

PVT was considered early [early portal vein thrombosis (e-PVT)] when it occurred within 30 days of transplantation, and it was considered late [late portal vein thrombosis (l-PVT)] when it was established after this period. If the patient developed any kind of PVT (early and/or late), he was also included in the total portal vein thrombosis (t-PVT) group. Patients who had clinical and laboratory signs suggestive of PVT (ascites, hypersplenism, an enlarged spleen, a low platelet count < 100,000/ mm3, and gastrointestinal bleeding) underwent Doppler US as the first diagnostic step for the detection of PVT. After the first postoperative day, there were no protocol Doppler US examinations during the follow-up, and further examinations were performed when they were

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clinically indicated. Additionally, abdominal computed tomography with reconstruction of the portal system was performed for cases with l-PVT.

Studied Variables The studied variables were as follows: diagnosis (BA versus other diseases), recipient BW, recipient age, Pediatric End-Stage Liver Disease (PELD) score, graftto-recipient weight ratio (GRWR), type of living donor liver graft (left lateral segment, left lobe, or other), use of VGs for PV reconstruction, type of VG, volume of packed red blood cell (PRBC) transfusions (mL/kg), cold ischemia time, and warm ischemia time. The incidence of e-PVT, l-PVT, and t-PVT and the use of VGs for PV reconstruction were studied in time periods divided into quintiles since the beginning of this series.

Statistical Analysis

Figure 1. Techniques used for portal reconstruction. (A) The liver graft’s PV is anastomosed in an end-to-end fashion to the recipient’s portal trunk. (B) An interposition VG is used between the recipient’s SMV/SV confluence and the donor’s PV.

Figure 2.

Means and medians were calculated to summarize continuous effects and were compared with t tests or appropriate nonparametric tests when distributional assumptions were in doubt. Categorical variables were expressed as numbers and percentages. Differences between groups were assessed with the chisquare test or Fisher’s exact test as needed. A univariate Cox proportional hazards model of the predictor variables was created, and those found to be significant at P < 0.10 were selected for the multivariate analysis. The final multivariate model was obtained with a forward selection method. The survival analysis was conducted according to the Kaplan-Meier product limit estimates, and patient subgroups were compared with a 2-sided log-rank test. All analyses were performed with the SPSS 21.0 statistical package (IBM, Inc., Chicago, IL).

Portal reconstruction with interposition VGs: (A) LDIMV and (B) DDIA.

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LIVER TRANSPLANTATION, October 2014

TABLE 1. Univariate Analysis of t-PVT After LDLT t-PVT Characteristic Age (months)* Weight (kg)* Sex: female [n (%)] Diagnosis [n (%)] BA Other PELD score* Liver graft [n (%)] Left lateral segment Left lobe Other VG [n (%)] Type of VG [n (%)] RIJV LDIMV DDIV LDOV DDIA GRWR (%)† Cold ischemia time (minutes)* Warm ischemia time (minutes)† PRBCs (mL/kg)*

No 14 (9-35) n 5 452 8.8 (7-13.5) n 5 452 251 (55.5) n 5 452 n 5 452 286 (63.3) 166 (36.7) 15 (9-21) n 5 376 n 5 451 377 (83.6) 57 (12.6) 17 (3.8) 61 (14.7) n 5 416 n 5 60 10 (16.7) 13 (21.7) 4 (6.7) 17 (28.3) 16 (26.7) 3.14 6 1.34 n 5 437 50 (32-80) n 5 452 38 6 12.3 n 5 452 17.3 (9.5-33.2) n 5 406

Yes 10.5 (8-15) n 5 34 7 (6-8.5) n 5 34 20 (58.8) n 5 34 n 5 34 31 (91.2) 3 (8.8) 17 (13-19) n 5 32 n 5 34 33 (97.1) 1 (2.9) 0 (0.0) 10 (29.4) n 5 34 n59 1 (11.1) 3 (33.3) 3 (33.3) 0 (0.0) 2 (22.3) 3.85 6 1.23 n 5 34 65 (30-120) n 5 25 43.5 6 9 n 5 25 31.4 (20-44.8) n 5 31

P Value 0.003 0.001 0.85

Analysis of factors associated with portal vein thrombosis in pediatric living donor liver transplant recipients.

The technique of vascular reconstruction plays a major role in the outcome of living donor liver transplantation (LDLT). An increased use of vascular ...
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